What is Multiple Sclerosis?

Multiple Sclerosis (MS) is a chronic, inflammatory and neurodegenerative human disease which results from the autoimmune destruction of myelin and associated collateral tissue damage within the human central nervous system.

MS affects approximately 2.5 million persons worldwide. In the United States, MS is the most common cause of non-traumatic, long-term neurological disability in young adults, affecting at least 400,000 persons. Although MS is found throughout the world, marked regional variability is well known and likely reflects a combination of multiple interacting genetic and environmental influences. MS is usually first noted in young adults, affecting women two to three times more frequently than men.

Despite the common description of MS as one disease, several subtypes are recognized clinically. The established clinical subtypes include: relapsing-remitting (RRMS), primary progressive (PPMS), secondary progressive (SPMS), and progressive-relapsing (PRMS) forms. Over decades most untreated persons with RRMS will become ?secondarily progressive?; i.e. will develop SPMS. At least 85% of the entire MS population is represented within the combined categories of RRMS and its subsequent form, SPMS. Persons with primary progressive MS (PPMS) are those who never have relapses and remissions, and comprise about 10% of all persons with MS. Progressive-relapsing MS (PRMS) is progressive from the onset without remission and is later punctuated with relapses and remissions. This form of MS affects about 5% of persons with MS.

A common individual course of MS is shown in the figure. As shown, the first clinical evidence of RRMS is usually preceded by subclinical disease activity most sensitively detected by changes in magnetic resonance imaging (MRI) of the brain. Eighty to 90% of new MRI events may not cause clinical symptoms perhaps due to their relatively small size, preferential distribution within the brain white matter, and redundancy of brain circuitry.

A new MRI event is an area of inflammation which is typically detected with a gadolinium (Gd)-enhanced MRI of the brain or spinal cord. After a period of a few weeks, the inflammation subsides, leaving an area of scar tissue (sclerosis) behind. The descriptive diagnostic term ?multiple sclerosis? derives from the multiplicity of these scarred (sclerotic) areas accumulated over time.

Clinical relapses can be associated with a variety of symptoms due to MS-related damage in brain and spinal cord. These may include disturbances of sensation, limb weakness, changes in vision or speech, balance or coordination problems, bowel and bladder control problems, excessive fatigue, and cognitive problems. As more inflammatory events occur over time, some of which actually reach clinical prominence (clinical relapses), the overall clinical and MRI extent of disease mounts (as shown in the Figure, white and orange lines, respectively).

At the same time, and now known to begin at even the earliest stages of MS, brain tissue loss also starts to occur, especially in untreated individuals. These changes correlate with long term irreversible physical and cognitive disabilities seen in many persons with MS. After 10 years disease duration, approximately 50% of untreated RRMS individuals will transition to SPMS.

This evolution is currently only recognizable after slow clinical worsening is noted in the absence of clinical relapses. All of these processes together lead to gradual MS worsening such that half of untreated persons with MS require a walking aid after 15-20 years of illness. The goals of early treatment of persons with MS are to help prevent the accumulation of brain and spinal cord damage that results in the disabling features of MS.